Phosphotyrosine accounts for about 0.5% of the total phosphoamino acid content of the cell and yet there is a wealth of evidence that tyrosine phosphorylation plays a crucial role in many cell regulatory processes. It is therefore not surprising to see that functional perturbation of protein tyrosine kinase (PTK) and protein phosphatases results in many diseases. Despite their importance, very little is known about the substrate specificity and mechanisms of action of PTKs. Using the "one-bead one-compound" combinatorial library method, we have successfully identified several efficient and specific peptide substrates for PTK. Based on these peptide substrate motifs, pseudo-substrate based peptide inhibitors were developed. In this project, we are using MidasPlus and other molecular modelling techniques to examine the molecular interactions between these peptide ligands and the enzyme. Additionaly, we are using Kuntz's DOCK 4.0 program to discover possible small molecule inhibitors for the enzyme. Inhibitors identified for c-src PTK may be therapeutic for osteoporosis and some cancers.